Rheumatoid arthritis (RA) is an autoimmune disease that primarily attacks synovial joints. Recent research has shown that the RA patient population is heterogeneous and that certain autoantibodies can be used as biomarkers to classify subgroups of RA patients and predict different courses of disease progression for different patient subgroups.
Autoantibodies directed against citrullinated proteins (ACPAs) are established biomarkers in RA and are, e.g., included in the 2010 American College of Rheumatology/European League Against Rheumatism criteria for RA (see, e.g., Aletaha D. et al., 2010, Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann. Rheum. Dis. 2010, 69, 1580-1588). RA patients forming ACPAs generally experience a more severe disease course, have a lower chance to enter drug-free remission and are subject to a different set of environmental and genetic risk factors than RA patients not forming ACPAs.
Recently, a second class of autoantibody biomarkers for RA has been discovered that complements the diagnostic and prognostic information provided by ACPAs. Research has shown that a more severe disease course can be predicted in ACPA-negative RA patients based on the detection of autoantibodies directed against carbamylated proteins (anti-CarP antibodies). The presence of anti-CarP antibodies is associated with more radiological progression of RA and with the conversion of non-inflammatory joint pain (arthralgia) to clinically manifested RA, which can ultimately result in a chronic, systemic inflammatory disorder.
Anti-CarP antibodies can be detected in serum samples many years prior to the onset of clinical symptoms of RA. Early detection of anti-CarP antibodies can enable at-risk RA candidates or early-stage RA patients to take preventative measures to ameliorate, delay or avert the onset of RA. However, the further development of anti-CarP antibodies as diagnostic and prognostic biomarkers in RA is hindered by the limitations of existing anti-CarP antibody assays.
Thus there is a need for new methods to detect anti-CarP antibodies. The present disclosure addresses this need by providing new compositions and methods for the development of anti-CarP antibody assays and provides related advantages as well.